As part of the NIH Eastern Regional Comprehensive Metabolomics Resource Core, scientists at RTI International and the David H. Murdock Research Institute (DHMRI) worked collaboratively on a study to use NMR-based metabolomics to identify key metabolic differences between hormone-responsive and triple negative breast cancer (TNBC). The findings were recently published in the Journal of Proteome Research.

TNBC, so called because of the absence of estrogen, progesterone and HER2/neu receptors on the tumor surface, is an aggressive form of breast cancer that accounts for 20 percent of all breast cancer cases. A higher percentage of those cases occur in African American women. TNBC responds poorly to some commonly used cancer treatments such as the chemotherapeutic drug paclitaxel (Taxol®).

“Our goal,” commented Kevin Knagge, PhD, Group Leader of the DHMRI Analytical Sciences Laboratory, “was to see which biological pathways are significantly different in TNBC cell lines versus other breast cancer lines and can, therefore, be targeted for alternative therapeutic intervention. This approach was novel as there are a limited number of reports in the literature regarding the use of NMR-based metabolomics.”

Study Findings

The study was based on the comparison of two hormone receptor-negative TNBC cell lines and two hormone receptor-positive Luminal A cell lines in the presence and absence of paclitaxel. The cell lines were originally derived from African American and Caucasian American women. RTI conducted the cell culture experiments and cytokine assays while DHMRI performed the NMR analyses. The two institutes work together to analyze the resulting data.

The scientists found that among other differences, the TNBC cell lines had higher levels of amino acids, nucleotides, and nucleotide sugars and lower levels of proliferation-related metabolites like choline compared with Luminal A cell lines,” and that the most significant differences distinguishing the cell types were related to amino acid, lipid and carbohydrate metabolism pathways.

DHMRI Scientist and study co-author Jason Winnike, PhD, added that the scientists “are continuing to analyze the data to look at other aspects of the metabolic signatures” and emphasized that the findings support the use of NMR-based metabolomics as a tool to identify new and potentially more effective therapeutic targets for TNBC drug development.